Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta
Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta
复制标题
DOI：
10.1016/j.placenta.2007.12.010
复制
发表时间：
2008-03-01
期刊：
影响因子：
3.8
通讯作者：
Mouzon, S. Hauguel-de
中科院分区：
文献类型：
--
作者：
Challier, J. C.;Basu, S.;Mouzon, S. Hauguel-de
肥胖和怀孕与胰岛素抵抗和炎症变化相关，而炎症变化会加剧。基于脂肪组织和胎盘的炎症转录组之间的相似性，我们假设胎盘因肥胖而产生过度的炎症。本研究的目的是表征与肥胖症周围炎症相关的胎盘炎症介质和巨噬细胞积累。使用免疫组织化学、流式细胞术以及巨噬细胞标记物和炎症细胞因子的表达，对来自 20 名肥胖女性和 15 名瘦女性的胎盘巨噬细胞和母体外周血单核细胞 (PBMC) 进行功能和表型表征。与瘦女性相比，肥胖女性胎盘中常驻CD68(+)和CD14(+)细胞的数量增加了2-3倍。巨噬细胞群的特点是具有明显的表型异质性，具有复杂的 CD14(+)、CD68(+) 和 CD11b(+) (mac-1) 细胞亚群，并且促炎细胞因子 IL-1、TNF-α、IL-6 的表达增加。胎盘炎症与 PBMC 基因表达的激活相关，并且母体但胎儿 PBMC 中的单核细胞分化和成熟标记物 CD14 和 CD68 增加。与瘦女性相比，肥胖女性的炎症变化与较高的血浆 C 反应蛋白和 IL-6 浓度相关。总之，妊娠前肥胖的慢性炎症状态随着胎盘中异质巨噬细胞群和促炎介质的积累而延伸到子宫内。由此产生的胎儿发育的炎症环境可能对肥胖的短期和长期规划产生严重后果。 (c) 2008 Elsevier Ltd. 保留所有权利。
Obesity and pregnancy are associated with a combination of insulin resistance and inflammatory changes which exacerbate in combination. Based on the similarity between the inflammatory transcriptomes of adipose tissue and placenta, we hypothesized that the placenta develops exaggerated inflammation in response to obesity. The aim of this study was to characterize placental inflammatory mediators and macrophage accumulation in relation to peripheral inflammation in obesity. Placental macrophages and maternal peripheral blood mononuclear cells (PBMC) from 20 obese and 15 lean women were functionally and phenotypically characterized using immumohistochemistry, flow cytometry and expression for macrophage markers and inflammatory cytokines. The number of resident CD68(+) and CD14(+) cells was increased 2-3 fold in the placenta of obese as compared to lean women. The macrophage population was characterized by a marked phenotypic heterogeneity with complex subsets of CD14(+), CD68(+) and CD11b(+) (mac-1) cells and by an increased expression of the pro-inflammatory cytokines IL-1, TNF-alpha, IL-6. Placental inflammation was associated with an activation of PBMC gene expression with an increase in the monocyte differentiation and maturation markers CD14 and CD68 in maternal but not fetal PBMC. The inflammatory changes were associated with higher plasma concentrations of C-reactive protein and IL-6 in obese compared to lean women.In conclusion, the chronic inflammation state of pre-gravid obesity is extending to in utero life with accumulation of a heterogeneous macrophage population and pro-inflammatory mediators in the placenta. The resulting inflammatory milieu in which the fetus develops may have critical consequences for short and long term programming of obesity. (c) 2008 Elsevier Ltd. All rights reserved.